Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function

doi:10.1046/j.1365-2125.2003.02034.x

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Wiley InterScience

British Journal of Clinical Pharmacology

Volume 57 Issue 4, Pages 393 - 401

Published Online: 7 Jan 2004

The Journal of The British Pharmacological Society

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Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function

Ingrid M. C. Kamerling , Aernout D. van Haarst , Jacobus Burggraaf , Rik C. Schoemaker , Marieke L. de Kam , Hartmut Heinzerling ¹ , Adam F. Cohen & Ad A. M. Masclee ²

Centre for Human Drug Research, Leiden, the Netherlands, ¹ Johnson & Johnson Pharmaceutical Research and Development, Janssen-Cilag, High Wycombe, UK, and ² Leiden University Medical Centre, Department of Gastroenterology, Leiden, the Netherlands

Correspondence to Aernout D van Haarst, Centre for Human Drug Research (CHDR), Zernikedreef 10, 2333 CL Leiden, the Netherlands. Tel: + 31 71 524 6420 Fax: + 31 71 524 6499 E-mail: avh@chdr.nl

KEYWORDS

antagonist • human and barostat • motilin • stomach

Aim

To assess the effects of the motilin receptor antagonist RWJ-68023 on basal and motilin-stimulated proximal gastric volume.

Methods

Eighteen healthy male volunteers received RWJ-68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ-68023 concentrations were assessed by radioimmunoassay and liquid chromatography-mass spectrometry, respectively.

Results

Both dosages of RWJ-68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ-68023 did not affect basal proximal gastric volume, but the high-dose RWJ-68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ-68023 was only significant (P = 0.014) during the distension procedure.

Conclusions

The RWJ-68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ-68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.

Received
3 July 2003
Accepted6
October 2003

DIGITAL OBJECT IDENTIFIER (DOI)

10.1046/j.1365-2125.2003.02034.x About DOI